In the years since my laboratory at the NIDA IRP identified the sigma-1 receptor in 1982, many preclinical studies have shown that sigma-1 receptors and associated ligands are involved in stroke, amnesia, depression, cancer, Alzheimers disease, pain, and cocaine addiction. In this fiscal year, we found that a transcription factor, Zinc finger protein 179, serves as the downstream signal of the sigma-1 receptor. This result link the action of sigma-1 receptor directly to gene expression. We also found that the sigma-1 receptor can regulate astrocytes that play important role in the neuronal activation and plasticity. In addition, we found that the sigma-1 receptor can bind to the dopamine transporter and facilitate the action of cocaine. Lastly, we found that the sigma-1 receptor agonist can potentiate the self-administration of cocaine. Thus, drugs that target the sigma-1 receptor may be of therapeutic value in treating cocaine addiction.